CN1326514A - Electrode strips for testing small volumes - Google Patents
Electrode strips for testing small volumes Download PDFInfo
- Publication number
- CN1326514A CN1326514A CN99813160A CN99813160A CN1326514A CN 1326514 A CN1326514 A CN 1326514A CN 99813160 A CN99813160 A CN 99813160A CN 99813160 A CN99813160 A CN 99813160A CN 1326514 A CN1326514 A CN 1326514A
- Authority
- CN
- China
- Prior art keywords
- test strip
- electrode
- analyte
- enzyme
- liquid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/54—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving glucose or galactose
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/001—Enzyme electrodes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/001—Enzyme electrodes
- C12Q1/005—Enzyme electrodes involving specific analytes or enzymes
- C12Q1/006—Enzyme electrodes involving specific analytes or enzymes for glucose
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- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Engineering & Computer Science (AREA)
- General Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Analytical Chemistry (AREA)
- Biotechnology (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Emergency Medicine (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Battery Electrode And Active Subsutance (AREA)
- Investigating Or Analyzing Materials By The Use Of Electric Means (AREA)
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
- Eye Examination Apparatus (AREA)
- Polishing Bodies And Polishing Tools (AREA)
Abstract
一种测试条,其包括承载有效电极和对电极的支持体和一层材料,待测的小体积液体可以分布在所说的材料层内并且提供电极之间的接触,并且其中材料上涂布有分析物特异性试剂。材料层可以以带的方式方便提供,从中可以切割部分或顺序使用。A test strip comprising a support carrying an active electrode and a counter electrode and a layer of material in which a small volume of liquid to be tested can be distributed and provides contact between the electrodes, and wherein the material is coated There are analyte-specific reagents. Layers of material are conveniently provided in strips, from which sections can be cut or used sequentially.
Description
Invention field
The present invention relates to be used for the electrode strip of for example whole blood of testing small volumes.
Background of invention
Diabetes are a kind of modal endocrinopathys.The patient is their blood-glucose content of monitoring constantly.Usually to realize by using the little test strip that detects blood-glucose.
The most normal problem that runs into of test strip user is that the blood flow volume on the test strip is improper and the layout of blood on test strip is improper.A lot of devices tackle this problem by the sample chamber of using capillary action to fill.Sample is retained near the electrode, promotes the mensuration of specific analyte in the sample; Referring to EP-A-0170375 and US-A-5141868.
This class known device comprises the electrode that is deposited on the non-conductive substrate, be coated with on the electrode be specific at the reagent system of analyte and be contained in the cavity, the size of this cavity is small enough to permission and introduces for example sample of 2.5-3 μ L of volume by capillary action.The compact degree of these devices is subjected to manufacturing tolerance and by the restriction of its chemical attainable signal to noise ratio.
US-5820551 discloses a kind of test strip, and it comprises the carrying working electrode and to the support of electroplax and be coated on enzyme and amboceptor on the active electrode.Whole blood just can provide the conducting path between the electrode, and can measure the glucose concn in the blood.Active electrode contacts with whole blood sample, between do not insert film or other whole blood filter.
WO-A-98/55856 (open after the application's priority date) discloses a kind of analyte specific reagent that is coated on the conducting stratum, and is positioned at reagent and the monofilament screen cloth above the reference electrode.The sample administration zone is provided at an edge of screen cloth.
Summary of the invention
First aspect of the present invention is a kind of test strip, it comprises the support and the layer of material of carrying active electrode and counter electrode, small volumes of liquids to be measured can be distributed in the said material layer and contact between the electrode is provided, and wherein be coated with the analyte specific reagent on the material, as a kind of component of redox reaction, for example enzyme, cofactor or amboceptor.Specifically, the invention provides a kind of test strip that is used for blood-glucose, wherein the demand of sample is considerably less, and by using reagent to realize effective reaction kinetics in new ways.
The material of reagent coating itself can be belt-like form.The flexibility band that second aspect of the present invention is material, liquid can be distributed in wherein and zone of dispersion thereon is coated with at least a component of redox reaction.
Invention is described
Among the present invention, any or various ingredients of redox reaction, for example enzyme (as notatin or glucose dehydrogenase), cofactor and amboceptor can be applied on the screen cloth or film that is placed on device top.Only for illustrational purpose, the present invention can be described as a reference with the screen cloth of enzyme coating.No matter use which kind of component or which component, when adding sample, they dissolve rapidly and form effective reaction medium, and this reaction medium can provide the contact between the test strip discrete electrodes.In this mode, diffusion barrier can be carried out and not have to reaction fast.This reaction type is low at sample volume, sample glues (as whole blood) and require in the quick response situation necessary especially.
In a typical embodiments of the present invention, the sensing member test strip is made up of two electrodes, one of them play the working electrode effect and another play oppositely, the reference electrode effect.The end of the working electrode that contacts with sample have one with its amboceptor that closely contacts.Test strip provides effectively by these two reaction chambers that electrode and additional lamella limited, and wherein said lamella overlays on above the electrode, and its precoating has the cofactor of any necessity of oxydo-reductase and enzyme.Reaction chamber can also comprise other sheet of material and/or wetting agent such as tensio-active agent or molten born of the same parents' material (it can be positioned on any one deck and cover in the lamella).In this way, organized enzyme is not coated on the conductor that forms working electrode but is provided in the above the separating layer, and this separating layer effectively forms the solution phase of reaction chamber again.When combining, can set up and approach in stirring reaction chamber, to carry out effective blended condition with lateral flow.
In an example of the present invention, silver chloride/silver-colored reference/counter electrode is placed on and is adjacent to carbon electrode.In general, for this purpose, a pair of printing carbon electrode is printed on the non-conductive substrate, silver/silver chloride is printed on makes it play the function of reference/counter electrode on one of them carbon electrode then.With non-conducting ink printing at carbon electrode with above the substrate so that determine in each electrode a part as on the contact mat that is used to insert gauger and each electrode away from another part of contact mat as the sensing unit that receives sample.
Then, preparation is used for the amboceptor of enzyme cofactor NADH, and by move liquid with its from the aqueous solution deposition to the electrode on.On working electrode, deposit the layer that another contains NAD then.
Give monofilament screen material coating surface promoting agent by moving spraying of liquid, printing ink or dip-coating, coating contains the solution of glucose dehydrogenase then, and be positioned over two electrodes above, form reaction chamber.This reaction chamber can also form the cavity that fill at the edge by additional printing or by using top layer to limit.For example, second kind of non-conducting ink printing at the top of screen material, applied a cover tape at the screen cloth top then in some way, so that stay enlarged area for the screen cloth of using the sample exposure.
This device allows the sample of small volume (in general be 1 μ L or still less) is applied to the extension of screen cloth.Next use the sensing unit of the exuberant device of sample, it is closely contacted with the mensuration electrode.
Unit describe with edge filling is in WO-A-98/55856.The present invention can simply change a social system them once.Specifically, can be with reference to Fig. 1 of WO-A-98/55856; Assembly of the present invention is support (1), electrode (2/3), screen material (6) and band (7); In addition, on screen material, provide reagent.This device can be worked by its edge is applied to sample.When sample was difficult to extract, it was valuable especially.Other structure is apparent to those skilled in the art, comprises being applied to the combination of covering one or more cofactors, amboceptor or enzyme on screen cloth or the membrane layer.The selection of various combinations can be depending on the reaction kinetics of all cpds.
In another embodiment of this device, enzyme or amboceptor are coated on the lamella, cofactor and other amboceptor or enzyme directly are coated on the working electrode, and lamella can filtering whole blood, so that active electrode detects the sample that does not effectively contain complete blood cell.At this moment, reduced result's hematocrit dependence basically.In this way, the rapid kinetics that has some or all reactive behavior compositions (enzyme, amboceptor and cofactor) in the filter born of the same parents function that can make selected film and the film combines, and obtains device efficiently.
In a word, device of the present invention makes up by needed one or more reagent of analyte quantitative analysis being deposited as individual layer or answering layer on fine screen mesh material or film; The size of deposition region is small enough to very the sample of small volume just can be wetting.This screen cloth or film both can also can use in electrochemical appliance in colorimetric device.
One of the present invention is characterised in that reagent accurately is coated on the target area of textile materials such as polyester or nylon or other porous-film.During use, it is provided at the quick dissolving of reagent under the existence of sample.A kind of reagent or plurality of reagents can be applied to obtain in accurate location with in clear and definite impression in the different methods of deposition known volume.Comprise the use partitioning device, as piston pump, syringe pump or request formula ink-jet printer.
In another embodiment, can be with the flexibility band that contains one or more reagent and the another kind of flexible tape lamination that is printed with a series of electrodes on it.The laminate that can use in order (containing a row or an a series of sensing member) is for example distributed by suitable divider, replaces cutting out single sensing member.For this purpose, no matter whether be laminate, the form of a band of the present invention with volume can be provided, and leave in the cartridge (cassette) of sealing, can also contain siccative in this cartridge.During use, cartridge can be inserted in the automatic dispenser, therefrom automatically the roll coil of strip be opened by indexing mechanism, order is exposed discrete sensing member.Therefore, the effect of this instrument is similar to the effect of photographic camera film.In this embodiment, band can also contain erythrolysis reagent such as saponin(e, so that reduce hematocrit and oxyphorase effect in the whole blood sample.Band can also further be avoided moisture effects by covering with the film (as the aluminium film) that can peel off, and divides timing when being with from cartridge, and the film that can peel off is peeled off automatically.When with sample administration during in sensing member, electrochemically in the working sample at the amount of analyte.This mensuration can be undertaken by currently known methods.
Following embodiment will illustrate the present invention.
Embodiment
By silk screen print method the conductive ink material is printed on the non-conducting polyester sheet layer material.The conductive ink material is made up of graphite and carbon granule and the mixture that is dissolved in the polymer binder of organic solvent.After treating the conductivity ink deposition, in forcing air oven, remove and desolvate.Silver/silver chloride reference/counter electrode is printed onto on the electrode of every pair of printing carbon electrode, then republishes non-conducting ink lay, so that determine contact mat and sensing member district.
To deposit on the carbon electrode such as amboceptor or other suitable dyestuff and the enzyme cofactor Reduced nicotinamide-adenine dinucleotide (NAD) of Meldola Blue, Nile Blue.Perhaps, with NAD by aqueous ink separately be coated to amboceptor above.
The form of enzyme glucose dehydrogenase with uniform round dot is deposited on the monofilament polyester screen cloth band.It can followingly obtain:
(a) in contact mode, allow the drop that is in close proximity to screen cloth that forms at the divider top end be transferred on the screen cloth by drop being touched screen surface; Perhaps
(b) in noncontact mode, the drop that allows ink jet printing head above the screen cloth or other hole form never can cause its distance that is seeped in the screen cloth to drip on the screen cloth
After the drying, round dot spreads and covers a zone, and this area part is determined by application conditions by screen cloth braiding feature and part.In general, the zone of 500nL drop covering is 1.3 * 1.2mm.Make the screen cloth band at room temperature dry.
Then, will further protect on the modification lamella of the screen cloth tape lamination auto levelizer of enzyme-modified and by non-conduction printing.Finally, cover tape is laminated to the top of screen cloth.The device lamella cuts conglobate single assembly.In another device form, laminated lamella rolled and the cartridge type unit of packing in, by being similar to the winding machinery of photographic camera film winding system, allow to use one device.
Claims (11)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9824627.5 | 1998-11-11 | ||
| GBGB9824627.5A GB9824627D0 (en) | 1998-11-11 | 1998-11-11 | Test strips for small volumes |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1326514A true CN1326514A (en) | 2001-12-12 |
Family
ID=10842191
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN99813160A Pending CN1326514A (en) | 1998-11-11 | 1999-11-11 | Electrode strips for testing small volumes |
Country Status (12)
| Country | Link |
|---|---|
| EP (1) | EP1129211B1 (en) |
| JP (1) | JP2002529717A (en) |
| KR (1) | KR20010092723A (en) |
| CN (1) | CN1326514A (en) |
| AT (1) | ATE244767T1 (en) |
| AU (1) | AU1063900A (en) |
| BR (1) | BR9915211A (en) |
| CA (1) | CA2351066A1 (en) |
| DE (1) | DE69909503T2 (en) |
| ES (1) | ES2203202T3 (en) |
| GB (1) | GB9824627D0 (en) |
| WO (1) | WO2000028068A1 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101074963B (en) * | 2006-05-17 | 2011-07-06 | 聿新生物科技股份有限公司 | Electrochemical cholesterol detection electrode test strip and manufacturing method thereof |
| CN105556299A (en) * | 2013-09-11 | 2016-05-04 | 西拉格国际有限责任公司 | Electrochemical-based analytical test strip with ultra-thin discontinuous metal layer |
| CN107664658A (en) * | 2016-07-27 | 2018-02-06 | 希森美康株式会社 | Electrode and manufacture method, enzyme/glucose sensor and biotic component measure device |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050103624A1 (en) | 1999-10-04 | 2005-05-19 | Bhullar Raghbir S. | Biosensor and method of making |
| GB0019694D0 (en) * | 2000-08-11 | 2000-09-27 | Cambridge Sensors Ltd | Electrochemical strip test for small volumes |
| JP4522014B2 (en) * | 2001-04-18 | 2010-08-11 | パナソニック株式会社 | Biosensor sheet, biosensor cartridge, and biosensor dispensing device |
| US6855243B2 (en) | 2001-04-27 | 2005-02-15 | Lifescan, Inc. | Electrochemical test strip having a plurality of reaction chambers and methods for using the same |
| CA2392980A1 (en) * | 2002-07-11 | 2004-01-11 | Lifescan, Inc. | Electrochemical test strip having a plurality of reaction chambers and methods for using the same |
| US7749437B2 (en) | 2003-06-20 | 2010-07-06 | Roche Diagnostics Operations, Inc. | Method and reagent for producing narrow, homogenous reagent stripes |
| US8148164B2 (en) | 2003-06-20 | 2012-04-03 | Roche Diagnostics Operations, Inc. | System and method for determining the concentration of an analyte in a sample fluid |
| US8206565B2 (en) | 2003-06-20 | 2012-06-26 | Roche Diagnostics Operation, Inc. | System and method for coding information on a biosensor test strip |
| US7645373B2 (en) | 2003-06-20 | 2010-01-12 | Roche Diagnostic Operations, Inc. | System and method for coding information on a biosensor test strip |
| US8058077B2 (en) | 2003-06-20 | 2011-11-15 | Roche Diagnostics Operations, Inc. | Method for coding information on a biosensor test strip |
| US8071030B2 (en) | 2003-06-20 | 2011-12-06 | Roche Diagnostics Operations, Inc. | Test strip with flared sample receiving chamber |
| US7604721B2 (en) | 2003-06-20 | 2009-10-20 | Roche Diagnostics Operations, Inc. | System and method for coding information on a biosensor test strip |
| US7718439B2 (en) | 2003-06-20 | 2010-05-18 | Roche Diagnostics Operations, Inc. | System and method for coding information on a biosensor test strip |
| US7645421B2 (en) | 2003-06-20 | 2010-01-12 | Roche Diagnostics Operations, Inc. | System and method for coding information on a biosensor test strip |
| US7452457B2 (en) | 2003-06-20 | 2008-11-18 | Roche Diagnostics Operations, Inc. | System and method for analyte measurement using dose sufficiency electrodes |
| US7597793B2 (en) | 2003-06-20 | 2009-10-06 | Roche Operations Ltd. | System and method for analyte measurement employing maximum dosing time delay |
| GB0322099D0 (en) * | 2003-09-20 | 2003-10-22 | Cambridge Sensors Ltd | Method for the reduction of Haematocrit effect on test strips and biosensors |
| US9012232B2 (en) | 2005-07-15 | 2015-04-21 | Nipro Diagnostics, Inc. | Diagnostic strip coding system and related methods of use |
| EP1756557B1 (en) | 2004-05-21 | 2017-03-15 | Agamatrix, Inc. | Method of making an electrochemical cell |
| US7556723B2 (en) | 2004-06-18 | 2009-07-07 | Roche Diagnostics Operations, Inc. | Electrode design for biosensor |
| US7569126B2 (en) | 2004-06-18 | 2009-08-04 | Roche Diagnostics Operations, Inc. | System and method for quality assurance of a biosensor test strip |
| WO2006059241A2 (en) * | 2004-11-05 | 2006-06-08 | Albatros Technologies Gmbh & Co. Kg | Analyte sensing device mounted on a flexible substrate |
| US8999125B2 (en) | 2005-07-15 | 2015-04-07 | Nipro Diagnostics, Inc. | Embedded strip lot autocalibration |
| US20080020452A1 (en) * | 2006-07-18 | 2008-01-24 | Natasha Popovich | Diagnostic strip coding system with conductive layers |
| GB2469070A (en) * | 2009-03-31 | 2010-10-06 | Diamatrix Ltd | Test material and cassette for bio-sensing |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4218421A (en) * | 1978-08-18 | 1980-08-19 | Honeywell Inc. | Disposable container for a continuous band of test strips |
| EP0230472B2 (en) * | 1985-06-21 | 2000-12-13 | Matsushita Electric Industrial Co., Ltd. | Biosensor and method of manufacturing same |
| US5169600A (en) * | 1987-07-15 | 1992-12-08 | Fuji Photo Film Co., Ltd. | Biochemical analysis apparatus for incubating and analyzing test sites on a long tape test film |
| GB8817421D0 (en) * | 1988-07-21 | 1988-08-24 | Medisense Inc | Bioelectrochemical electrodes |
| DE4326339A1 (en) * | 1993-08-05 | 1995-02-09 | Boehringer Mannheim Gmbh | System for analysis of sample liquids |
| US5762770A (en) * | 1994-02-21 | 1998-06-09 | Boehringer Mannheim Corporation | Electrochemical biosensor test strip |
| US5779867A (en) * | 1994-10-07 | 1998-07-14 | Biomedix, Inc. | Dry chemistry glucose sensor |
| US5628890A (en) * | 1995-09-27 | 1997-05-13 | Medisense, Inc. | Electrochemical sensor |
| US5798031A (en) * | 1997-05-12 | 1998-08-25 | Bayer Corporation | Electrochemical biosensor |
| US6764581B1 (en) * | 1997-09-05 | 2004-07-20 | Abbott Laboratories | Electrode with thin working layer |
-
1998
- 1998-11-11 GB GBGB9824627.5A patent/GB9824627D0/en not_active Ceased
-
1999
- 1999-11-11 JP JP2000581234A patent/JP2002529717A/en active Pending
- 1999-11-11 DE DE69909503T patent/DE69909503T2/en not_active Expired - Fee Related
- 1999-11-11 WO PCT/GB1999/003764 patent/WO2000028068A1/en not_active Ceased
- 1999-11-11 CN CN99813160A patent/CN1326514A/en active Pending
- 1999-11-11 AU AU10639/00A patent/AU1063900A/en not_active Abandoned
- 1999-11-11 CA CA002351066A patent/CA2351066A1/en not_active Abandoned
- 1999-11-11 ES ES99954225T patent/ES2203202T3/en not_active Expired - Lifetime
- 1999-11-11 EP EP99954225A patent/EP1129211B1/en not_active Expired - Lifetime
- 1999-11-11 BR BR9915211-8A patent/BR9915211A/en not_active IP Right Cessation
- 1999-11-11 KR KR1020017005806A patent/KR20010092723A/en not_active Withdrawn
- 1999-11-11 AT AT99954225T patent/ATE244767T1/en not_active IP Right Cessation
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101074963B (en) * | 2006-05-17 | 2011-07-06 | 聿新生物科技股份有限公司 | Electrochemical cholesterol detection electrode test strip and manufacturing method thereof |
| CN105556299A (en) * | 2013-09-11 | 2016-05-04 | 西拉格国际有限责任公司 | Electrochemical-based analytical test strip with ultra-thin discontinuous metal layer |
| CN107664658A (en) * | 2016-07-27 | 2018-02-06 | 希森美康株式会社 | Electrode and manufacture method, enzyme/glucose sensor and biotic component measure device |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1129211B1 (en) | 2003-07-09 |
| EP1129211A1 (en) | 2001-09-05 |
| WO2000028068A1 (en) | 2000-05-18 |
| GB9824627D0 (en) | 1999-01-06 |
| ES2203202T3 (en) | 2004-04-01 |
| DE69909503T2 (en) | 2004-01-29 |
| BR9915211A (en) | 2001-10-30 |
| KR20010092723A (en) | 2001-10-26 |
| AU1063900A (en) | 2000-05-29 |
| DE69909503D1 (en) | 2003-08-14 |
| ATE244767T1 (en) | 2003-07-15 |
| CA2351066A1 (en) | 2000-05-18 |
| JP2002529717A (en) | 2002-09-10 |
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